Type 1 interferons (IFNs) were the first cytokines discovered and include IFNβ, more than ten forms of IFNα, and several other related molecules that all bind to the same type 1 IFN receptor (IFN1R). Type 1 IFNs are commonly referred to as “viral” IFNs because they can be induced directly by virus infections, in contrast to “immune” IFN, or IFNγ, which is synthesized after receptor engagement of T cells and natural killer (NK) cells during immune responses. Type 1 IFNs get induced by viral nucleic acids and proteins acting on cellular signaling molecules such as Toll-like receptors and RNA helicases, which, in turn, release transcription factors into the nucleus. Mice lacking IFN1R appear normal in a pathogen-free environment but are extraordinarily susceptible to virus infections. This susceptibility is partially due to IFN-regulated genes that suppress viral replication, but type 1 IFNs also have many immunoregulatory properties that could also affect host susceptibility to infection.